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조회296

충남대학교

Redox Biol., May 17 2024, 73 S2213-2317(24)00171-X | https://doi.org/10.1016/j.redox.2024.103193 The absence of thioredoxin-interacting protein in alveolar cells exacerbates asthma during obesity

Ji-Soo Jeong ^a,1, Jeong-Won Kim ^a,1, Jin-Hwa Kim ^a, Chang-Yeop Kim ^a,b, Eun-Hye Chung ^a, Young-Eun Cho^c, Eui-Ju Hong ^a, Hyo-Jung Kwon ^a, Je-Won Ko^a, Tae-Won Kim^a

^aCollege of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, 99 Daehak-ro, Daejeon, 34131, Republic of Korea

^bInhalation Toxicology, Jeongeup Campus, KIT, Jeongeupsi, Jelabukdo, 580-185, Republic of Korea

^cAndong National University, Andong, 36729, Republic of Korea

¹J.S.J. and J.W.K. (Jeong-Won Kim) contributed equally to this work.

Corresponding authors: Je-Won Ko, Tae-Won Kim

Abstract

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIP ^Cre) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIP ^Cre mice, despite being TXNIP deficient, TXNIP ^Cre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-27)
연구진국내 연구진
분야 생명과학 > 수의학

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